The present invention relates to novel pesticides of the formula (I) below having improved action against parasites; to compositions suitable for use as parasiticides comprising those compounds as active ingredient and to methods of controlling parasites that are based on the administration of those compounds or compositions, and to the use of the said compounds and compositions in a method of controlling parasites and in the manufacture of pesticides for use against parasites. Also described are intermediates of formula (XX) which themselves have parasiticidal activity and are excellently suitable for the preparation of compounds of formula (I).
Numerous pesticides are known that can be used in controlling parasites on warm-blooded animals. The control is effected principally by two different methods; either by way of contact action by topical and therefore external treatment of the host animal or systemically, that is to say by oral, transdermal or percutaneous administration to the host animal and ingestion of the active ingredient by the parasites via the blood of the host animal.
Far fewer substances are available for systemic use than for topical application, because only substances that have a systemic action and are well tolerated by the host animal can be used.
Compounds having as characteristic structural element the sub-structure of formula (II) 
wherein R1, X, Y, T and U are as defined for formula (I) hereinbelow, form a very interesting class of substances on account of their pronounced topical and systemic action.
A prominent individual example is nitenpyram, a compound of formula (III) 
Nitenpyram and other examples of this class of substances are disclosed, together with their preparation, in EP 0 302 389. Those compounds are described as pesticides having very pronounced insecticidal activity. Further examples of this class of substances are, for example, the subjects of the following patent applications: European published specifications Nos. 285 985; 302 833; 376 279; 471 372; 364 844; 493 369; 381 130; 529 680; 163 855; 375 907; 259 738; 386 565; 383 091 and 590 425; U.S. Pat. Nos. 5 063 236; 5 302 605 and 4 742 060; and also DE-4 207 604; GB-2 228 003 and WO 93/24002. Certain substituted 4-nitroimino-perhydro-1.3.5-oxadiazine derivatives and the use as pesticides and intermediates are described in WO 98/06710.
Nitenpyram and other examples of this class of substances that have the said structural element of formula (II) are extremely effective when administered as contact pesticides, for example externally, that is to say topically, to an infested host animal where they come into direct contact with the parasites. They also, however, exhibit a good systemic immediate action when they are administered to the infested host animal orally, parenterally, via injection or via implant.
The action, which is pronounced per se, has a serious disadvantage, however, in that it has been found that while the compounds have a high initial action, their action falls off rapidly only a short time after administration. This can be observed particularly clearly after systemic administration and can be monitored by reference to the bioavailability. Blood level measurements show that in many cases high blood levels are achieved even after a few minutes or, more rarely, after a few hours, but these levels then fall within a few hours, at best within a few days, and therefore fall to below an effective concentration much too rapidly.
In order to eliminate this shortcoming, numerous, but unfortunately unsuccessful, experiments have already been carried out. For example, it has been shown that a prolongation of the systemic action by increasing the dose can be achieved only to a limited extent. If, for example, depots sufficiently large for the active ingredient to be released over several weeks were to be placed under the skin or in the muscles, then the amounts to be injected or implanted would have to be so large that they would no longer be tolerated by the host animal; local irritation, skin eruptions and painful areas develop. This solution, possible per se, therefore fails on practical and, of course, also ethical grounds. Similarly, it has been found that a long-term action is not achievable by an increased oral dose.
When the known compounds having the structural element of formula (II) are administered, it is principally observed that a major part of the substance exhibits its full action only over a short period of time immediately after administration and thereafter the action very rapidly declines. This has serious consequences for preparations for use in veterinary medicine, for example for tablets, injections or for treatment using the pour-on or spot-on method. Because of the short duration of action it is necessary to repeat treatments at short intervals, which means that the keeper of the animal must either repeat the treatment himself, or have it carried out by a veterinary surgeon, at short intervals. Such an intensive treatment programme requires a high degree of discipline, however, and, as experience has shown, after only a short time gives rise to stress on the part of the animal and on the part of the animal""s keeper, which not infrequently results in aversion to the treatment and leads to its premature discontinuation.
Prolongation of the action of this inherently extremely effective class of substances has therefore long been a desirable but apparently unattainable goal. The problem underlying the present invention was to achieve that goal and provide substances suitable for use as pesticides having significantly improved properties, especially having a pronounced long-term action.
By the provision of the compounds of formula (I) below it has now, surprisingly, been possible for compounds having the structural element of formula (II) to be modified chemically in such a manner that a high degree of long-term bioavailability after administration is achieved without it being necessary to accept adverse effects as a result.
The new, improved compounds are compounds of formula (I) below 
wherein
R1 is hydrogen or a radical from the group C1-C4alkyl, formyl, C1-C6alkylcarbonyl, C1-C4-alkylsulfonyl, aryl, arylsulfonyl, arylcarbonyl, heterocyclyl and heterocyclyl-substituted C1-C6alkyl, which radical is unsubstituted or mono- or poly-substituted by identical or different substituents; the said substituents being C1-C4alkyl, C1-C4alkoxy, C1-C4alkyl-thio, C1-C4haloalkyl, halogen, hydroxy, cyano, nitro, amino, C1-C4alkylamino, (C1-C4-alkyl)2amino, alkoxycarbonyl, C1-C4alkylsulfonyl and arylsulfonyl;
X is CH or N;
Y is an electron-withdrawing radical, preferably cyano, nitro or C1-C6haloalkyl-carbonyl, especially COxe2x80x94CF3;
T has the meanings of R1 or together with U forms a C1-C4alkylene bridge which is unsubstituted or substituted by a radical R1, or T and U together with the group xe2x80x94Nxe2x80x94Cxe2x80x94Nxe2x80x94 form a saturated or unsaturated 5- or 6-membered heterocyclic ring which may in addition contain as further hetero atom O or S or the hetero group xe2x80x94N(C1-C6alkyl)xe2x80x94;
U is hydrogen or C1-C6alkyl, preferably hydrogen, methyl or ethyl;
R2 is hydrogen or C1-C6alkyl; R2xe2x80x2 is hydrogen or C1-C6alkyl; and
R is C1-C20alkyl, C2-C20alkenyl, C2-C6alkynyl or heterocyclyl, each of those radicals being unsubstituted or substituted by one or more identical or different substituents, the said substituents being selected from the group halogen, cyano, nitro, hydroxy, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C6haloalkoxy and phenyl; or is C3-C7cycloalkyl that is unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C20haloalkoxy and phenyl; wherein each phenyl moiety is itself unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6alkoxy,
C1-C6alkylthio, C1-C6haloalkyl and C1-C20haloalkoxy; or is phenyl phenoxyphenyl each of which is unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, and C1-C20haloalkoxy.
Within the scope of formula (I) above, preference is given to compounds wherein R is C1-C20alkyl, C2-C20alkenyl or C2-C6alkynyl, each of those radicals being unsubstituted or mono- or poly-substituted by identical or different substituents, the said substituents being selected from the group halogen, cyano, nitro, hydroxy, C1-C6alkoxy, C1-C6alkylthio, C1-C6-haloalkyl, C1-C6haloalkoxy and phenyl; or is C3-C7cycloalkyl that is unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C20haloalkoxy and phenyl; or is phenyl phenoxyphenyl each of which is unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C20haloalkoxy.
Within the group of compounds of formula (I) wherein R is C3-C7cycloalkyl that is mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C20haloalkoxy and phenyl; wherein the phenyl moiety is itself unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl and C1-C20haloalkoxy, special preference on account of their pronounced activity is given to those compounds in which the C3-C7cycloalkyl radical is substituted by one substituent and in the 1-position.
By the introduction of the side chain of formula (IV) 
wherein R2, R2xe2x80x2 and R are as defined for formula (I), it has now been possible to prepare substances that exhibit simultaneously a number of long sought and very desirable properties and are now actually suitable for practical use:
1. The compounds of formula (I) have a high level of activity against arthropods, especially blood-sucking insects.
2. They exhibit excellent tolerability when administered systemically and topically to a host animal.
3. They are distinguished by an appreciably longer duration of action in comparison with known compounds having the structural element of formula (II), which can readily be demonstrated by reference to the mortality of the parasites on the host animal.
4. They can be handled satisfactorily from the standpoint of formulation technology and have adequate storage stability.
It was not to be predicted that the chemical modification carried out here would result in these advantageous properties and would be able to impart to the novel compounds of formula (I) these positive long-term properties.
In the context of the present invention, the definitions of the substituents are to be understood as follows: each of the substituents indicated under formula (I) that can itself be poly-substituted is substituted by either identical or different substituents, that is to say multiple substitutions are to be interpreted as meaning that identical or different substituents can be present simultaneously on the same radical. For example, a radical poly-substituted by halogen may have either several identical halogen atoms or several different halogen atoms. Multiple substitutions are to be interpreted accordingly for other radicals.
The alkyl groups appearing in the definitions of substituents in terms such as alky, alkylcarbonyl, alkylsulfonyl, alkoxy, alkylthio, haloalkyl, alkylamino, dialkylamino, haloalkylcarbonyl, etc. may, according to the number of carbon atoms, be straight-chain or branched and are, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl, octadecyl or eicosyl, and the branched isomers thereof, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl. Alkoxy, haloalkyl, haloalkylcarbonyl and haloalkoxy radicals are derived from the mentioned alkyl groups and accordingly are partially or fully halogenated radicals; poly-halogenated radicals carry identical or different halogen atoms.
The terms halo and halogen denote halogen atoms and generally denote fluorine, chlorine, bromine or iodine, here preferably fluorne or chlorine, as substituent of an alkyl group especially fluorine and as substituent of a heterocycle especially chlorine.
Examples of haloalkylxe2x80x94as a group per se and as a structural element of other groups and compounds, such as haloalkoxyxe2x80x94are methyl mono- to tri-substituted by fluorine, chlorine and/or bromine, such as CHF2 or CF3; ethyl mono- to penta-substituted by fluorine, chlorine and/or bromine, such as CH2CF3, CF2CF3, CF2CCl3, CF2CHCl2, GF2CHF2, CF2CFCl2, CF2CHBr2, CF2CHClF, CF2CHBrF or CClFCHClF; propyl or isopropyl mono- to hepta-substituted by fluorine, chlorine and/or bromine, such as CH2CHBrCH2Br, CF2CHFCF3, CH2CF2CF3 or CH(CF3)2; and butyl mono- to nona-substituted by fluorine, chlorine and/or bromine, or one of its isomers, such as CF(CF3)CHFCF3 or CH2(CF2)2CF3.
In the context of the present invention, Het and heterocyclyl are to be understood as meaning aliphatic or aromatic cyclic radicals that contain at least one oxygen, sulfur or nitrogen atom. Five- and six-membered heterocycles are preferred. Heterocyclyl accordingly typically includes substituents such as dioxolanyl, pyrrolidinyl, piperidinyl, morpholinyl, pyridyl, pyrrolyl, furyl, thienyl, imidazolyl, tetrahydrofuryl, tetrahydropyranyl, dihydrofuryl, dihydropyranyl, isoxazolyl, oxazolyl, thiazolyl, oxazolinyl, oxazolidinyl, imidazolinyl, imidazolidinyl and dioxanyl. Special preference is given to those which are unsubstituted or contain one or two halogen atoms, halogen here being fluorine, chlorine or bromine, but especially chlorine. Of those heterocyclic radicals special mention should be made of pyridyl, thiazolyl and tetrahydrofuryl. More especially preferred sub-groups of formula (I) contain as heterocyclyl radicals 5,6-dichloro-pyridin-3-yl, 6-chloro-pyridin-3-yl, 2-chlorothiazol-5-yl and tetrahydrofuran-3-yl.
Aryl by itself or as part of a substituent, for example arylsulfonyl, arylcarbonyl or aralkyl, is phenyl or naphthyl, preferably phenyl.
Alkenyl is, in each case giving due consideration to the number of carbon atoms contained in the group in question, either straight-chain, e.g. vinyl, 1-methyMnyl, allyl, 1-butenyl or 2-hexenyl, or branched, e.g. isopropenyl. Alkynyl is, in each case giving due consideration to the number of carbon atoms contained in the group in question, either straight-chain, e.g. propargyl, 2-butynyl or 5-hexynyl, or branched, e.g. 2-ethynylpropyl or 2propargylisopropyl. C3-C7Cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
Typical C1-C4alkylene bridges are xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94, CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94, xe2x80x94CH(CH3)xe2x80x94CH2xe2x80x94, xe2x80x94CH(C2H5)xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH(CH3)xe2x80x94CH2xe2x80x94, xe2x80x94CH(CH3)xe2x80x94CH(CH3)xe2x80x94, xe2x80x94C(CH3)2xe2x80x94, xe2x80x94C(CH3)(C2H5) and xe2x80x94C(C2H5)2xe2x80x94.
Compounds of formula (I) having at least one basic centre may form acid addition salts with strong acids. Physiologically tolerable acid addition salts are of special interest.
An interesting sub-group within the compounds according to the invention is formed by compounds of formula (I) wherein
Y is NO2;
R1 is hydrogen or a radical from the group C1-C4alkyl, formyl, C1-C4alkylcarbonyl, C1-C4-alkylsulfonyl, aryl, arylsulfonyl, arylcarbonyl, heterocyclyl and heterocyclyl-substituted C1-C6alkyl, which radical is unsubstituted or mono- or poly-substituted by identical or different substituents; the said substituents being C1-C4alkyl, C1-C4alkoxy, C1-C4alkylthio, C1-C4haloalkyl, halogen, hydroxy, cyano, nitro, amino, C1-C4alkylamino, (C1-C4-alkyl)2amino, alkoxycarbonyl, C1-C4alkylsulfonyl and arylsulfonyl;
T has the meanings of R1 or together with U forms a C1-C4alkylene bridge which is unsubstituted or substituted by a radical R1, or T and U together with the group xe2x80x94Nxe2x80x94Cxe2x80x94Nxe2x80x94 form a saturated or unsaturated 5- or 6-membered heterocyclic ring which may in addition contain as further hetero atom O or S or the hetero group xe2x80x94N(C1-C6alkyl)xe2x80x94;
U is hydrogen or C1-C6alkyl, preferably hydrogen, methyl or ethyl; and R2, R2xe2x80x2 and R are as defined for formula (I).
Another interesting group is formed by compounds of formula (I) wherein
R1 is xe2x80x94CH2xe2x80x94Het; X is CH; Y is NO2;
Het is heterocyclyl that is unsubstituted or mono- or poly-substituted by identical or different substituents; the substituents being C1-C4alkyl, C1-C4alkoxy, C1-C4alkylthio, C1-C4haloalkyl, halogen, hydroxy, cyano, nitro, amino, C1-C4alkylamino, (C1-C4alkyl)2amino, alkoxycarbonyl, C1-C4alkylsulfonyl and arylsulfonyl;
T (1) is a radical from the group formyl, C1-C6alkylcarbonyl, C1-C4alkylsulfonyl, aryl, arylsulfonyl, arylcarbonyl, heterocyclyl and heterocyclyl-substituted C1-C6alkyl, which radical is unsubstituted or mono- or poly-substituted by identical or different substituents; the said substituents being C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, halogen, hydroxy, cyano, nitro, amino, C1-C4alkylamino, (C1-C4alkyl)2amino, C1-C4alkylsulfonyl and arylsulfonyl; or
(2) T together with U forms a C1-C4alkylene bridge which is unsubstituted or substituted by a radical selected from the group C1-C4alkyl, formyl, C1-C6alkylcarbonyl, C1-C4alkylsulfonyl, aryl, arylsuffonyl, arylcarbonyl, heterocyclyl and heterocyclyl-substituted C1-C6-alkyl; each radical from the said group itself being unsubstituted or substituted by C1-C4alkyl, C1-C4alkoxy, C1-C4haloalkyl, halogen, hydroxy, cyano, nitro, amino, C1-C4-alkylamino, (C1-C4alkyl)2amino, C1-C4alkylsulfonyl or arylsulfonyl; or
(3) T and U together with the group xe2x80x94Nxe2x80x94Cxe2x80x94Nxe2x80x94 form a saturated or unsaturated 5- or 6-membered heterocyclic ring which may in addition contain as further hetero atom O or S or the hetero group xe2x80x94N(C1-C6alkyl)xe2x80x94;
U is hydrogen or C1-C6alkyl, preferably hydrogen, methyl or ethyl; and R2, R2xe2x80x2 and R are as defined for formula (I).
Very especially preferred within the scope of formula (I), however, are compounds of formula (X) 
wherein
R1 is xe2x80x94CH2-Het;
R is C1-C20alkyl, C2-C20alkenyl or C2-C6alkynyl, each of those radicals being unsubstituted or mono- or poly-substituted by identical or different substituents, the said substituents being selected from the group halogen, cyano, nitro, hydroxy, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C6haloalkoxy and phenyl; or is C3-C7cycloalkyl that is unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C20haloalkoxy and phenyl; or is phenyl phenoxyphenyl each of which is unsubstituted or mono- or poly-substituted by identical or different substituents selected from halogen, cyano, nitro, hydroxy, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6haloalkyl, C1-C20haloalkoxy;
T and U are each independently of the other hydrogen or C1-C6alkyl, preferably hydrogen, methyl or ethyl;
R2 is hydrogen or C1-C6alkyl; R2xe2x80x2 is hydrogen or C1-C6alkyl; and
Het is heterocyclyl that is unsubstituted or mono- or poly-subsfituted by identical or different halogen atoms.
A further especially preferred sub-group of compounds of formula (I) is formed, on account of their pronounced activity, by compounds of formula (XI) 
wherein
Hal is halogen, preferably fluorine, chlorine or bromine and especially chlorine; and especially occupies the 6-position in the pyridine;
X is CH or N and especially N;
Y is an electron-withdrawing radical, preferably cyano, nitro or C1-C6haloalkyl-carbonyl, especially COxe2x80x94CF3; more especially nitro;
T together with U forms a C1-C4alkylene bridge, preferably an ethylene bridge, which is preferably unsubstituted or substituted by methyl or ethyl; and R2, R2xe2x80x2 and R are as defined for formula (I).
Equally preferred on account of their pronounced activity is a sub-group of compounds of formula (I) having the following formula (XII) 
wherein
Hal is halogen, preferably fluorine, chlorine or bromine and especially chlorine; and especially occupies the 2-position in the thiazole;
X is CH or N and especially N;
Y is an electron-withdrawing radical, preferably cyano, nitro or C1-6haloalkyl-carbonyl, especially COxe2x80x94CF3; more especially nitro;
T together with U forms one of the groups xe2x80x94CH2xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94Oxe2x80x94CH2xe2x80x94 and xe2x80x94CH2xe2x80x94N(CH3)CH2xe2x80x94, wherein all methylene groups are unsubstituted or one of said methylen groups is substituted by methyl or ethyl; and R2, R2xe2x80x2 and R are as defined in claim 1 for formula (I).
A preferred sub-group of compounds within the scope of formula (X) is formed by those compounds wherein U is methyl or ethyl.
A further preferred group of compounds within the scope of formula (X) is formed by those compounds wherein T is methyl or ethyl.
A further preferred sub-group of compounds within the scope of formula (X) is formed by those compounds wherein R2 and R2xe2x80x2 are hydrogen, methyl or ethyl.
Especially preferred among the compounds within the scope of formula (X) and within the scope of preferred sub-groups mentioned above are those compounds in which the radical Het is pyridyl, thiazolyl or tetrahydrofuryl that is unsubstituted or mono- or di-substituted by halogen; especially 5,6-dichloro-pyridin-3-yl, 6-chloro-pyridin-3-yl, 2-chlorothiazol-5-yl and tetrahydrofuran-3-yl.
Within the scope of mentioned sub-groups, preference is given to compounds of formula (I) wherein R is C1-C20alkyl, C2-C20alkenyl or C2-C6alkynyl and especially straight-chain or branched C6-C20alkyl.
Especially preferred on account of its biological activity is any compound selected from the group of compounds 1.001; 1.008; 1.011; 1.012; 1.013; 1.014; 1.015; 1.018; 1.019; 1.020; 1.021; 1.022; 1.054; 1.055; 1.056; 1.057; 1.058; 1.059; 1.060; 1.061; 1.062; 1.063; 1.064; 1.065; 1.066; 1.067; 1.068; 1.069; 1.070; 1.071; 1.072; 1.073; 1.074; 1.075; 1.076; 1.077; 1.078; 1.079; 1.080; 1.081; 1.082; 1.083; 1.084; 1.085; 1.086 and 1.087.
Parasites in the context of the present invention are parasitic arthropods and, of those, especially blood-sucking insects. Insects of the following orders are included: Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. Special mention should also be made, however, of pests that trouble human beings or animals and transmit pathogens, for example flies, such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia caniculadis, Sarcophaga carnaria, Lucilia sericata, Ludlia cuptina, Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Callipora erythrocephala (=blowfly), Haematobia (=hornfly) and mosquitos, and also blood-sucking pests, for example fleas, such as Ctenocephalides felis and Ctenocephalides canis (cat and dog fleas), Xenopsylla cheopis, Pulex irritans, Dermatophilus penetrans, lice, such as Damalina ovis, Pediculus humanis, stable flies and horseflies, such as Stomoxys calcitrans, Haematopota pluvialis, Tabanus nigrovittatus, Chrysops caecutiens, tabanids, tsetse flies, such as Glossinia species, and biting insects, more especially cockroaches, such as Blatella germanic or Blatta orientalis, Periplaneta americana. The said parasites attack warm-blooded animals, including farm animals, such as cows, pigs, sheep and goats, poultry, such as hens, turkeys and geese, animals bred for their fur, such as mink, foxes, chinchillas, rabbits and the like, as well as domestic animals and pets, such as cats and dogs, and even human beings do not escape attack.
Likewise, flea infestation in domestic animals and pets is a problem for the animal owner to which as yet only unsatisfactory solutions have been found. Owing to the complicated life cycle of the flea, none of the known methods of controlling fleas is totally satisfactory, especially since most of the known methods are aimed principally at controlling the fully grown fleas in the animal""s coat and take no account at all of the various juvenile stages of the fleas, which live not only in the animal""s coat but also on the floor, on carpets, on the animal""s sleeping place, on chairs, in the garden and in all the other places with which the infested animal comes into contact. Flea treatment is generally expensive and must be continued for a prolonged period, success generally only being achieved when the treatment is applied not only to the infested animal, e.g. the dog or cat, but also simultaneously to any places frequented by the infested animal.
The compounds of formula (I) according to the invention can be used alone or in combination with other biocides. For example, in order to increase the effect they can be combined with pesticides having the same direction of action or in order to broaden the spectrum of action they can be combined with substances having a different direction of action. It may also be of advantage to add repelling substances, so-called repellents. Where it is desired to extend the spectrum of action to endoparasites, e.g. worms, the compounds of formula (I) are advantageously combined with substances having endoparasiticidal properties. They can, of course, also be used in combination with anti-bacterial agents. Since the compounds of formula (I) are xe2x80x9cadulticidesxe2x80x9d, that is to say since they are effective especially against the fully grown stages of the target parasites, the addition of pesticides that are effective rather against the juvenile stages of the parasite may be very advantageous, since in that way the majority of parasites causing large-scale economic damage will be covered. Furthermore, a substantial contribution is made to avoiding the development of resistance. Some combinations may also lead to synergistic effects, that is to say the total amount of active ingredient applied can be reduced, which is desirable from the ecological standpoint. Preferred groups of combination partners and especially preferred combination partners are given below, it being possible for the combinations to comprise one or more of these partners in addition to a compound of formula (I).
Suitable mixing partners include biocides, for example the insecticides and acaricides listed below, which have various mechanisms of action and are well known to the person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients that act in the same way as juvenile hormones; active ingredients that act as adulticides; broad spectrum insecticides; broad spectrum acaricides and nematicides; and also the well known anthelmintics and substances that repel insects and/or acarina, the afore-mentioned repellents or detachers.
Non-limiting examples of suitable insecticides and acaricides are:
(I) aldicarb;
(II) azinphos-methyl;
(III) benfuracarb;
(IV) bifenthrin;
(V) buprofezin;
(VI) carbofuran;
(VII) dibutylaminothio;
(VIII) cartap;
(IX) chlorfluazuron;
(X) chlorpyrifos;
(XI) cyfluthrin;
(XII) lambda-cyhalothrin;
(XIII) alpha-cypermethrin;
(XIV) zeta-cypermethrin;
(XV) deltamethrin;
(XVI) diflubenzuron;
(XVII) endosulfan;
(XVIII) ethiofencarb;
(XIX) fenitrothion;
(XX) fenobucarb;
(XXI) fenvalerate;
(XXII) formothion;
(XXIII) methiocarb;
(XXIV) heptenophos;
(XXV) imidacloprid;
(XXVI) isoprocarb;
(XXVII) methamidophos;
(XXVIII) methomyl;
(XXIX) mevinphos;
(XXX) parathion;
(XXXI) parathion-methyl;
(XXXII) phosalone;
(XXXIII) pirimicarb;
(XXXIV) propoxur,
(XXXV) teflubenzuron;
(XXXVI) terbufos;
(XXXVII) triazamate;
(XXXVIII) abamectin;
(XXXIX) fenobucarb;
(XL) tebufenozide;
(XLI) fipronil;
(XLII) beta-cyfluthrin;
(XLIII) silafluofen;
(XLIV) fenpyroximate;
(XLV) pyridaben;
(XLVI) fenazaquin;
(XLVII) pyriproxyfen;
(XLVIII) pyrimidifen;
(XLIX) nitenpyram;
(L) NI-25, acetamiprid;
(LI) avermectin B1;
(LII) an insect-active extract from a plant;
(LIII) a preparation containing insect-active nematodes;
(LIV) a preparation obtainable from Bacillus subtilis;
(LV) a preparation containing insect-active fungi;
(LVI) a preparation containing insect-active viruses;
(LVII) AC 303 630;
(LVIII) acephat;
(LIX) acrinathrin;
(LX) alanycarb;
(LXI) alphamethrin;
(LXII) amitraz;
(LXIII) AZ 60541;
(LXIV) azinphos A;
(LXV) azinphos M;
(LXVI) azocyclotin;
(LXVII) bendiocarb;
(LXVIII) bensultap;
(LXIX) beta-cyfluthrin;
(LXX) BPMC;
(LXXI) brofenprox;
(LXXII) bromophos A;
(LXXIII) bufencarb;
(LXXIV) butocarboxime;
(LXXV) butylpyridaben;
(LXXVI) cadusafos;
(LXXVII) carbaryl;
(LXXVIII) carbophenothion;
(LXXIX) chloethocarb;
(LXXX) chlorethoxyfos;
(LXXXI) chlormephos;
(LXXXII) cis-Res-methrin;
(LXXXIII) clocythrin;
(LXXXIV) clofentezin;
(LXXXV) cyanophos;
(LXXXVI) cycloprothrin;
(LXXXVII) cyhexatin;
(LXXXVIII) demeton M;
(LXXXIX) demeton S;
(XC) demeton-S-methyl;
(XCI) dichlofenthion;
(XCII) dicliphos;
(XCIII) diethion;
(XCIV) dimethoat;
(XCV) dimethylvinphos;
(XCVI) dioxathion;
(XCVII) edifenphos;
(XCVIII) emamectin;
(XCIX) esfenvalerat;
(C) ethion;
(CI) ethofenprox;
(CII) ethoprophos;
(CIII) etrimphos;
(CIV) fenamiphos;
(CV) fenbutatinoxid;
(CVI) fenothiocarb;
(CVII) fenpropathrin;
(CVIII) fenpyrad;
(CIX) fenthion;
(CX) fluazinam;
(CXI) flucycloxuron;
(CXII) flucythrinat;
(CXIII) flufenoxuron;
(CXIV) flufenprox;
(CXV) fonophos;
(CXVI) fosthiazat;
(CXVII) fubfenprox;
(CXVIII) HCH;
(CXIX) hexaflumuron;
(CXX) hexythiazox;
(CXXI) iprobenfos;
(CXXII) isofenphos;
(CXXIII) isoxathion;
(CXXIV) ivermectin;
(CXXV) lambda-cyhalothrin;
(CXXVI) malathion;
(CXXVII) mecarbam;
(CXXVIII) mesulfenphos;
(CXXIX) metaldehyd;
(CXXX) metolcarb;
(CXXXI) milbemectin;
(CXXXII) moxidectin;
(CXXXIII) naled;
(CXXXIV) NC 184;
(CXXXV) omethoat;
(CXXXVI) oxamyl;
(CXXXVII) oxydeme- thon M;
(CXXXVIII) oxydeprofos;
(CXXXIX) permethrin;
(CXL) phenthoat;
(CXLI) phorat;
(CXLII) phosmet;
(CXLIII) phoxim;
(CXLIV) pirimiphos M;
(CXLV) pirimiphos A;
(CXLVI) promecarb;
(CXLVII) propaphos;
(CXLVIII) prothiofos;
(CXLIX) prothoat;
(CL) pyrachlophos;
(CLI) pyrada-phenthion;
(CLII) pyresmethrin;
(CLIII) pyrethrum;
(CLIV) RH 5992;
(CLV) salithion;
(CLVI) sebufos;
(CLVII) sulfotep;
(CLVIII) sulprofos;
(CLIX) tebufenpyrad;
(CLX) tebupirimphos;
(CLXI) tefluthrin;
(CLXII) temephos;
(CLXIII) terbam;
(CLXIV) tetrachlorvinphos;
(CLXV) thiafenox;
(CLXVI) thiodicarb;
(CLXVII) thiofanox;
(CLXVIII) thionazin;
(CLXIX) thuringiensin;
(CLXX) tralomethrin;
(CLXXI) triarthen;
(CLXXII) triazophos;
(CLXXIII) triazuron;
(CLXXIV) trichlorfon;
(CLXXV) triflumuron;
(CLXXVI) trimethacarb;
(CLXXVII) vamidothion;
(CLXXVIII) xylylcarb;
(CLXXIX) YI 5301/5302;
(CLXXX) zetamethrin;
(CLXXXI) DPX-MP062;
(CLXXXII) RH-2485;
(CLXXXIII) D 2341;
(CLXXXIV) XMC (3,5,-xylyl methylcarbamate),
(CLXXXV) lufenuron
(CLXXXVI) fluazuron
(CLXXXVII) methoprene
(CLXXXVIII) hydroprene
(CLXXXIX) fenoxycarb
(CXC) chlorfenapyr or
(CSCI) spinosad
Non-limiting examples of suitable anthelmintics are mentioned below, some examples, in addition to having the anthelmintic activity, also having an insecticidal and acaricidal activity and, in some cases, being already contained in the list above:
(A1) praziquantel=2-cyclohexylcarbonyl-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-xcex1]isoquinoline
(A2) closantel=3,5-diiodo-N-[5-chloro-2-methyl-4-(a-cyano-4-chlorobenzyl)phenyl]salicylamide
(A3) triclabendazole=5-chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1H-benzimidazole
(A4) levamisol=L-(xe2x88x92)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1b]thiazole
(A5) mebendazole=(5-benzoyl-1H-benzimidazol-2-yl)carbamic acid methyl ester
(A6) omphalotin=a macrocyclic fermentation product of the fungus Omphalotus olearius described in WO 97/20857
(A7) abamectin=avermectin B1
(A8) ivermectin=22,23-dihydroavermectin B1
(A9) moxidectin=5-O-demethyl-28-deoxy-25-(1,3-dimethyl-1-butenyl)-6,28-epoxy-23-(methoxyimino)-milbemycin B
(A10) doramectin=25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-avermectin A1a
(A11) milbemectin=mixture of milbemycin A3 and milbemycin A4
(A12) milbemycinoxim=5-oxime of milbemectin
Non-limiting examples of suitable repelling substances (repellents or detachers) are:
(R1) DEET (N,N-diethyl-m-toluamide)
(R2) KBR 3023 N-butyl-2-oxycarbonyl-(2-hydroxy)-piperidine
(R3) cymiazole=N,-2,3-dihydro-3-methyl-1,3-thiazol-2-ylidene-2,4-xylidene
The said mixing partners are well known to experts in the field. Most of them are described in the various editions of the Pesticide Manual, The British Crop Protection Council, London, and others are described in the various editions of The Merck Index, Merck and Co., Inc., Rahway, N.J., USA or in the patent literature. The following list therefore confines itself to giving some examples of sources.
(I) 2-methyl-2-(methylthio)propionaldehyde-O-methylcarbamoyloxime (aldicarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 26;
(II) S-(3,4-dihydro-4-oxobenzo-[d]-[1,2,3]-triazin-3-ylmethyl)O,O-dimethyl-phosphorodithioate (azinphos-methyl), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 67;
(III) ethyl-N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl-(methyl)aminothio]-N-isopropyl-xcex2-alaninate (benfuracarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 96;
(IV) 2-methylbiphenyl-3-ylmethyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate (bifenthrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 118;
(V) 2-tert-butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazian-4-one (buprofezin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 157;
(VI) 2,3-dihydro-2,2-dimethylbenzofuran-7-yl-methylcarbamate (carbofuran), from The Pesticide Manual, 11thed. (1997), The British Crop Protection Council, London, page 186;
(VII) 2,3-dihydro-2,2-dimethylbenzofuran-7-yl-(dibutylaminothio)methylcarbamate (carbosulfan), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 188;
(VIII) S,Sxe2x80x2-(2-dimethylaminotrimethylene)-bis(thiocarbamate) (cartap), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 193;
(IX) 1-[3,5-dichloro-4-(3-chloro-5-trifluoromethyl-2-pyidyloxy)phenyl]-3-(2,6-difluorobenzoyl)urea (chlorfluazuron), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 213;
(X) O,O-diethyl-O-3,5,6-trichloro-2-pyridyl-phosphorothioate (chlorpyrifos), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 235;
(XI) (RS)-xcex1-cyano-4-fluoro-3-phenoxybenzyl-(1RS,3RS;1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (cyfluthrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 293;
(XII) mixture of (Sxe2x80x2)-xcex1-cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate and (R)-xcex1-cyano-3-phenoxybenzyl-(Z)-(1R,3R)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate (lambda-cyhalothrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 300;
(XIII) racemate consisting of (Sxe2x80x2)-xcex1-cyano-3-phenoxybenzyl-(1R,3R)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate and (R)-xcex1-cyano-3-phenoxybenzyl-(1S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (alpha-cypermethrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 308;
(XIV) a mixture of the stereoisomers of (S)-xcex1-cyano-3-phenoxybenzyl (1RS,3RS,1RS,3RS)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (zeta-cype rmethrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 314;
(XV) (S)-xcex1-cyano-3-phenoxybenzyl-(1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 344;
(XVI) (4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea (diflubenzuron), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 395;
(XVII) (1,4,5,6,7,7-hexachloro-8,9,10-trinorborn-5-en-2,3-ylenebismethylene)-sulfite (endosulfan), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 459;
(XVIII) xcex1-ethylthio-o-tolyl-methylcarbamate (ethiofencarb), from The Pesticide Manual, 11thed. (1997), The British Crop Protection Council, London, page 479;
(XIX) O,O-dimethyl-O-4-nitro-m-tolyl-phosphorothioate (fenitrothion), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 514;
(XX) 2-sec-butylphenyl-methylcarbamate (fenobucarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 516;
(XXI) (RS)-xcex1-cyano-3-phenoxybenzyl-(RS)-2-(4-chlorophenyl)-3-methylbutyrate (fenvalerate), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 539;
(XXII) S-[formyl(methyl)carbamoylmethyl]-O,O-dimethyl-phosphorodithioate (formothion), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 625;
(XXIII) 4-methylthio-3,5-xylyl-methylcarbamate (methiocarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 813;
(XXIV) 7-chlorobicyclo[3.2.0]hepta-2,6-dien-6-yl-dimethylphosphate (heptenophos), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 670;
(XXV) 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine (imidacloprid), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 706;
(XXVI) 2-isopropylphenyl-methylcarbamate (isoprocarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 729;
(XXVII) O,S-dimethyl-phosphoramidothioate (methamidophos), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 808;
(XXVIII) S-methyl-N-(methylcarbamoyloxy)thioacetimidate (methomyl), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 815;
(XXIX) methyl-3-(dimethoxyphosphinoyloxy)but-2-enoate (mevinphos), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 844;
(XXX) O,O-diethyl-O-4-nitrophenyl-phosphorothioate (parathion), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 926;
(XXXI) O,O-dimethyl-O-4-nitrophenyI-phosphorothioate (parathion-methyl), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 928;
(XXXII) S-6-chloro-2,3-dihydro-2-oxo-1,3-benzoxazol-3-ylmethyl-O,O-diethyl-phosphorodithioate (phosalone), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 963;
(XXXIII) 2-dimethylamino-5,6-dimethylpyrimidin-4-yl-dimethylcarbamate (pirimicarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 985;
(XXXIV) 2-isopropoxyphenyl-methylcarbamate (propoxur), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1036;
(XXXV) 1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea (teflubenzuron), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1158;
(XXXVI) S-tert-butylthiomethyl-O,O-dimethyl-phosphorodithioate (terbufos), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1165;
(XXXVII) ethyl-(3-tert-butyl-1-dimethylcarbamoyl-1H-1,2,4-triazol-5-yl-thio)-acetate, (triazamate), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1224;
(XXXVIII) abamectin, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 3;
(XXXIX) 2-sec-butylphenyl-methylcarbamate (fenobucarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 516;
(XL) N-tert-butyl-N-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide (tebufenozide), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1147;
(XLI) (xc2x1)-5-amino-1-(2,6-dichloro-xcex1,xcex1,xcex1-trifluoro-p-tolyl)-4-trifluoromethyl-sufinylpyrazole-3-carbonitrile (fipronil), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 545;
(XLII) (RS)-xcex1-cyano-4-fluoro-3-phenoxybenzyl(1RS,3RS;1RS,3,RS3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (beta-cyfluthrin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 295;
(XLIII) (4-ethoxyphenyl)-[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane (silafluofen), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1105;
(XLIV) tert-butyl (E)-xcex1-(1,3-dimethyl-5-phenoxypyrazol-4-yl-methyleneamino-oxy)-p-toluate (fenpyroximate), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 530;
(XLV) 2-tert-butyl-5-(4-tert-butylbenzylthio)-4-chloropyridazin-3(2H)-one (pyridaben), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1161;
(XLVI) 4-[[4-(1,1-dimethylphenyl)phenyl]ethoxy]-quinazoline (fenazaquin), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 507;
(XLVII) 4-phenoxyphenyl-(RS)-2-(pyridyloxy)propyl ether (pyriproxyfen), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1073;
(XLVIII) 5-chloro-N-{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpydmidine-4-amine (pyrimidifen), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1070;
(XLIX) (E)-N-(6-chloro-3-pyridylmethyl)-N-ethyl-N-methyl-2-nitrovinylidenediamine (nitenpyram), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 880;
(L) (E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1-methylacetamidine (NI-25, acetamiprid), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 9;
(LI) avermectin B1, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 3;
(LII) an insect-active extract from a plant, especially (2R,6aS,12aS)-1,2,6,6a,12,12a-hexahydro-2-isopropenyl-8,9-dimethoxy-chromeno[3,4-b]furo[2,3-h]chromen-6-one (rotenone), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1097; and an extract from Azadirachta indica, especially azadirachtin, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 59; and
(LIII) a preparation containing insect-active nematodes, preferably Heterorhabditis bacteriophora and Heterorhabditis megidis, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 671; Steinemema feltiae, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1115, and Steinemema scapterisci, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1116;
(LIV) a preparation, obtainable from Bacillus subtilis, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 72; or from a Bacillus thuringiensis strain with the exception of compounds isolated from GC91 or from NCTC11821; The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 73;
(LV) a preparation containing insect-active fungi, preferably Verticillium lecanii, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1266; Beauveria brogniartii, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 85; and Beauveria bassiana, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 83;
(LVI) a preparation containing insect-active viruses, preferably Neodipddon Sertifer NPV, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 759; and Cydia pomonella granulosis virus, from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 291;
(CLXXXI) 7-chloro-2,3,4a,5-tetrahydro-2-[methoxycarbonyl(4-trifluoromethoxyphenyl)carb amoyl]indol[1,2e]oxazoline-4a-carboxylate (DPX-MP062, indoxycarb), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 453;
(CLXXXII) Nxe2x80x2-tert-butyl-Nxe2x80x2-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide (RH-2485, methoxyfenozide), from The Pesticide Manual, 11th ed. (1997), The British Crop Protection Council, London, page 1094; and
(CLXXXIII) (Nxe2x80x2-[4-methoxy-biphenyl-3-yl]-hydrazinecarboxylic acid isopropyl ester (D 2341), from Brighton Crop Protection Conference, 1996, 487-493;
(R2) Book of Abstracts, 212th ACS National Meeting Orlando, Fla., Aug. 25-29 (1996), AGRO-020. Publisher: American Chemical Society, Washington, D.C. CONEN: 63BFAF.
In accordance with the above remarks, a further important aspect of the present invention relates to combination preparations for controlling parasites on warm-blooded animals which comprise, in addition to a compound of formula (I), at least one further active ingredient having the same or a different direction of action and at least one physiologically tolerable carrier. The present invention is not restricted to two-component combinations.
Within the scope of the present invention preference is given, for example, to the following two-component combinations, the figure in parenthesis representing one of the combination partners mentioned above and the number following the symbol xe2x80x9candxe2x80x9d representing a compound from the Tables which follow:
(IX) and 1.001; (IX) and 1.008; (IX) and 1.011; (IX) and 1.012; (IX) and 1.013; (IX) and 1.014; (IX) and 1.015; (IX) and 1.018; (IX) and 1.019; (IX) and 1.020; (IX) and 1.021; (IX) and 1.022; (IX) and 1.054; (IX) and 1.055; (IX) and 1.056; (IX) and 1.057; (IX) and 1.058; (XIII) and 1.001; (XIII) and 1.008; (XIII) and 1.011; (XIII) and 1.012; (XIII) and 1.013; (XIII) and 1.014; (XIII) and 1.015; (XIII) and 1.018; (XIII) and 1.019; (XIII) and 1.020; (XIII) and 1.021; (XIII) and 1.022; (XIII) and 1.054; (XIII) and 1.055; (XIII) and 1.056; (XIII) and 1.057; (XIII) and 1.058; (XIV) and 1.001; (XIV) and 1.008; (XIV) and 1.011; (XIV) and 1.012; (XIV) and 1.013; (XIV) and 1.014; (XIV) and 1.015; (XIV) and 1.018; (XIV) and 1.019; (XIV) and 1.020; (XIV) and 1.021; (XIV) and 1.022; (XIV) and 1.054; (XIV) and 1.055; (XIV) and 1.056; (XIV) and 1.057; (XIV) and 1.058; (LI) and 1.001; (LI) and 1.008; (LI) and 1.011; (LI) and 1.012; (LI) and 1.013; (LI) and 1.014; (LI) and 1.015; (LI) and 1.018; (LI) and 1.019; (LI) and 1.020; (LI) and 1.021; (LI) and 1.022; (LI) and 1.054; (LI) and 1.055; (LI) and 1.056; (LI) and 1.057; (LI) and 1.058; (XXV) and 1.001; (XXV) and 1.008; (XXV) and 1.011; (XXV) and 1.012; (XXV) and 1.013; (XXV) and 1.014; (XXV) and 1.015; (XXV) and 1.018; (XXV) and 1.019; (XXV) and 1.020; (XXV) and 1.021; (XXV) and 1.022; (XXV) and 1.054; (XXV) and 1.055; (XXV) and 1.056; (XXV) and 1.057; (XXV) and 1.058; (XXXV) and 1.001; (XXXV) and 1.008; (XXXV) and 1.011; (XXXV) and 1.012; (XXXV) and 1.013; (XXXV) and 1.014; (XXXV) and 1.015; (XXXV) and 1.018; (XXXV) and 1.019; (XXXV) and 1.020; (XXXV) and 1.021; (XXXV) and 1.022; (XXXV) and 1.054; (XXXV) and 1.055; (XXXV) and 1.056; (XXXV) and 1.057; (XXXV) and 1.058; (XXXVIII) and 1.001; (XXXVIII) and 1.008; (XXXVIII) and 1.011; (XXXVIII) and 1.012; (XXXVIII) and 1.013; (XXXVIII) and 1.014; (XXXVIII) and 1.015; (XXXVIII) and 1.018; (XXXVIII) and 1.019; (XXXVIII) and 1.020; (XXXVIII) and 1.021; (XXXVIII) and 1.022; (XXXVIII) and 1.054; (XXXVIII) and 1.055; (XXXVIII) and 1.056; (XXXVIII) and 1.057; (XXXVIII) and 1.058; (XLI) and 1.001; (XLI) and 1.008; (XLI) and 1.011; (XLI) and 1.012; (XLI) and 1.013; (XLI) and 1.014; (XLI) and 1.015; (XLI) and 1.018; (XLI) and 1.019; (XLI) and 1.020; (XLI) and 1.021; (XLI) and 1.022; (XLI) and 1.054; (XLI) and 1.055; (XLI) and 1.056; (XLI) and 1.057; (XLI) and 1.058; (XLVII) and 1.001; (XLVII) and 1.008; (XLVII) and 1.011; (XLVII) and 1.012; (XLVII) and 1.013; (XLVII) and 1.014; (XLVII) and 1.015; (XLVII) and 1.018; (XLVII) and 1.019; (XLVII) and 1.020; (XLVII) and 1.021; (XLVII) and 1.022; (XLVII) and 1.054; (XLVII) and 1.055; (XLVII) and 1.056; (XLVII) and 1.057; (XLVII) and 1.058; (XLIX) and 1.001; (XLIX) and 1.008; XLIX) and 1.011; (XLIX) and 1.012; (XLIX) and 1.013; (XLIX) and 1.014; (XLIX) and 1.015; (XLIX) and 1.018; (XLIX) and 1.019; (XLIX) and 1.020; (XLIX) and 1.021; (XLIX) and 1.022; (XLIX) and 1.054; (XLIX) and 1.055; (XLIX) and 1.056; (XLIX) and 1.057; (XLIX) and 1.058; (LXI) and 1.001; (LXI) and 1.008; (LXI) and 1.011; (LXI) and 1.012; (LXI) and 1.013; (LXI) and 1.014; (LXI) and 1.015; (LXI) and 1.018; (LXI) and 1.019; (LXI) and 1.020; (LXI) and 1.021; (LXI) and 1.022; (LXI) and 1.054; (LXI) and 1.055; (LXI) and 1.056; (LXI) and 1.057; (LXI) and 1.058; (LXII) and 1.001; (LXII) and 1.008; (LXII) and 1.011; (LXII) and 1.012; (LXII) and 1.013; (LXII) and 1.014; (LXII) and 1.015; (LXII) and 1.018; (LXII) and 1.019; (LXII) and 1.020; (LXII) and 1.021; (LXII) and 1.022; (LXII) and 1.054; (LXII) and 1.055; (LXII) and 1.056; (LXII) and 1.057; (LXII) and 1.058; (CIX) and 1.001; (CIX) and 1.008; (CIX) and 1.011; (CIX) and 1.012; (CIX) and 1.013; (CIX) and 1.014; (CIX) and 1.015; (CIX) and 1.018; (CIX) and 1.019; (CIX) and 1.020; (CIX) and 1.021; (CIX) and 1.022; (CIX) and 1.054; (ClX) and 1.055; (CIX) and 1.056; (CIX) and 1.057; (CIX) and 1.058; (CXIII) and 1.001; (CXIII) and 1.008; (CXIII) and 1.011; (CXIII) and 1.012; (CXIII) and 1.013; (CXIII) and 1.014; (CXIII) and 1.015; (CXIII) and 1.018; (CXIII) and 1.019; (CXIII) and 1.020; (CXIII) and 1.021; (CXIII) and 1.022; (CXIII) and 1.054; (CXIII) and 1.055; (CXIII) and 1.056; (CXIII) and 1.057; (CXIII) and 1.058; (CXIX) and 1.001; (CXIX) and 1.008; (CXIX) and 1.011; (CXIX) and 1.012; (CXIX) and 1.013; (CXIX) and 1.014; (CXIX) and 1.015; (CXIX) and 1.018; (CXIX) and 1.019; (CXIX) and 1.020; (CXIX) and 1.021; (CXIX) and 1.022; (CXIX) and 1.054; (CXIX) and 1.055; (CXIX) and 1.056; (CXIX) and 1.057; (CXIX) and 1.058; (CXXIV) and 1.001; (CXXIV) and 1.008; (CXXIV) and 1.011; (CXXIV) and 1.012; (CXXIV) and 1.013; (CXXIV) and 1.014; (CXXIV) and 1.015; (CXXIV) and 1.018; (CXXIV) and 1.019; (CXXIV) and 1.020; (CXXIV) and 1.021; (CXXIV) and 1.022; (CXXIV) and 1.054; (CXXIV) and 1.055; (CXXIV) and 1.056; (CXXIV) and 1.057; (CXXIV) and 1.058; (CXXXI) and 1.001; (CXXXI) and 1.008; (CXXXI) and 1.011; (CXXXI) and 1.012; (CXXXI) and 1.013; (CXXXI) and 1.014; (CXXXI) and 1.015; (CXXXI) and 1.018; (CXXXI) and 1.019; (CXXXI) and 1.020; (CXXXI) and 1.021; (CXXXI) and 1.022; (CXXXI) and 1.054; (CXXXI) and 1.055; (CXXXI) and 1.056; (CXXXI) and 1.057; (CXXXI) and 1.058; (CXXXII) and 1.001; (CXXXII) and 1.008; (CXXXII) and 1.011; (CXXXII) and 1.012; (CXXXII) and 1.013; (CXXXII) and 1.014; (CXXXII) and 1.015; (CXXXII) and 1.018; (CXXXII) and 1.019; (CXXXII) and 1.020; (CXXXII) and 1.021; (CXXXII) and 1.022; (CXXXII) and 1.054; (CXXXII) and 1.055; (CXXXII) and 1.056; (CXXXII) and 1.057; (CXXXII) and 1.058; (CXXXIX) and 1.001; (CXXXIX) and 1.008; (CXXXIX) and 1.011; (CXXXIX) and 1.012; (CXXXIX) and 1.013; (CXXXIX) and 1.014; (CXXXIX) and 1.015; (CXXXIX) and 1.018; (CXXXIX) and 1.019; (CXXXIX) and 1.020; (CXXXIX) and 1.021; (CXXXIX) and 1.022; (CXXXIX) and 1.054; (CXXXIX) and 1.055; (CXXXIX) and 1.056; (CXXXIX) and 1.057; (CXXXIX) and 1.058; (CLII) and 1.001; (CLII) and 1.008; (CLII) and 1.011; (CLII) and 1.012; (CLII) and 1.013; (CLII) and 1.014; (CLII) and 1.015; (CLII) and 1.018; (CLII) and 1.019; (CLII) and 1.020; (CLII) and 1.021; (CLII) and 1.022; (CLII) and 1.054; (CLII) and 1.055; (CLII) and 1.056; (CLII) and 1.057; (CLII) and 1.058; (CLIII) and 1.001; (CLIII) and 1.008; (CLIII) and 1.011; (CLIII) and 1.012; (CLIII) and 1.013; (CLIII) and 1.014; (CLIII) and 1.015; (CLIII) and 1.018; (CLIII) and 1.019; (CLIII) and 1.020; (CLIII) and 1.021; (CLIII) and 1.022; (CLIII) and 1.054; (CLIII) and 1.055; (CLIII) and 1.056; (CLIII) and 1.057; (CLIII) and 1.058; (CLIX) and 1.001; (CLIX) and 1.008; (CLIX) and 1.011; (CLIX) and 1.012; (CLIX) and 1.013; (CLIX) and 1.014; (CLIX) and 1.015; (CLIX) and 1.018; (CLIX) and 1.019; (CLIX) and 1.020; (CLIX) and 1.021; (CLIX) and 1.022; (CLIX) and 1.054; (CLIX) and 1.055; (CLIX) and 1.056; (CLIX) and 1.057; (CLIX) and 1.058; (CLXXIII) and 1.001; (CLXXIII) and 1.008; (CLXXIII) and 1.011; (CLXXIII) and 1.012; (CLXXIII) and 1.013; (CLXXIII) and 1.014; (CLXXIII) and 1.015; (CLXXIII) and 1.018; (CLXXIII) and 1.019; (CLXXIII) and 1.020; (CLXXIII) and 1.021; (CLXXIII) and 1.022; (CLXXIII) and 1.054; (CLXXIII) and 1.055; (CLXXIII) and 1.056; (CLXXIII) and 1.057; (CLXXIII) and 1.058; (CLXXV) and 1.001; (CLXXV) and 1.008; (CLXXV) and 1.011; (CLXXV) and 1.012; (CLXXV) and 1.013; (CLXXV) and 1.014; (CLXXV) and 1.015; (CLXXV) and 1.018; (CLXXV) and 1.019; (CLXXV) and 1.020; (CLXXV) and 1.021; (CLXXV) and 1.022; (CLXXV) and 1.054; (CLXXV) and 1.055; (CLXXV) and 1.056; (CLXXV) and 1.057; (CLXXV) and 1.058; (CLXXXI) and 1.001; (CLXXXI) and 1.008; (CLXXXI) and 1.011; (CLXXXI) and 1.012; (CLXXXI) and 1.013; (CLXXXI) and 1.014; (CLXXXI) and 1.015; (CLXXXI) and 1.018; (CLXXXI) and 1.019; (CLXXXI) and 1.020; (CLXXXI) and 1.021; (CLXXXI) and 1.022; (CLXXXI) and 1.054; (CLXXXI) and 1.055; (CLXXXI) and 1.056; (CLXXXI) and 1.057; (CLXXXI) and 1.058; (CLXXXV) and 1.001; (CLXXXV) and 1.008; (CLXXXV) and 1.011; (CLXXXV) and 1.012; (CLXXXV) and 1.013; (CLXXXV) and 1.014; (CLXXXV) and 1.015; (CLXXXV) and 1.018; (CLXXXV) and 1.019; (CLXXXV) and 1.020; (CLXXXV) and 1.021; (CLXXXV) and 1.022; (CLXXXV) and 1.054; (CLXXXV) and 1.055; (CLXXXV) and 1.056; (CLXXXV) and 1.057; (CLXXXV) and 1.058; (CLXXXVI) and 1.001; (CLXXXVI) and 1.008; (CLXXXVI) and 1.011; (CLXXXVI) and 1.012; (CLXXXVI) and 1.013; (CLXXXVI) and 1.014; (CLXXXVI) and 1.015; (CLXXXVI) and 1.018; (CLXXXVI) and 1.019; (CLXXXVI) and 1.020; (CLXXXVI) and 1.021; (CLXXXVI) and 1.022; (CLXXXVI) and 1.054; (CLXXXVI) and 1.055; (CLXXXVI) and 1.056: (CLXXXVI) and 1.057; (CLXXXVI) and 1.058; (CLXXXVII) and 1.001; (CLXXXVII) and 1.008: (CLXXXVII) and 1.011; (CLXXXVII) and 1.012; (CLXXXVII) and 1.013; (CLXXXVII) and 1.014; (CLXXXVII) and 1.015; (CLXXXVII) and 1.018; (CLXXXVII) and 1.019; (CLXXXVII) and 1.020; (CLXXXVII) and 1.021; (CLXXXVII) and 1.022; (CLXXXVII) and 1.054; (CLXXXVII) and 1.055; (CLXXXVII) and 1.056; (CLXXXVII) and 1.057; (CLXXXVII) and 1.058; (CLXXXVIII) and 1.001; (CLXXXVIII) and 1.008; (CLXXXVIII) and 1.011; (CLXXXVIII) and 1.012; (CLXXXVIII) and 1.013; (CLXXXVIII) and 1.014; (CLXXXVIII) and 1.015; (CLXXXVIII) and 1.018; (CLXXXVIII) and 1.019; (CLXXXVIII) and 1.020; (CLXXXVIII) and 1.021; (CLXXXVIII) and 1.022; (CLXXXVIII) and 1.054; (CLXXXVIII) and 1.055; (CLXXXVIII) and 1.056; (CLXXXVIII) and 1.057; (CLXXXVIII) and 1.058; (CLXXXIX) and 1.001; (CLXXXIX) and 1.008; (CLXXXIX) and 1.011; (CLXXXIX) and 1.012; (CLXXXIX) and 1.013; (CLXXXIX) and 1.014; (CLXXXIX) and 1.015; (CLXXXIX) and 1.018; (CLXXXIX) and 1.019; (CLXXXIX) and 1.020; (CLXXXIX) and 1.021; (CLXXXIX) and 1.022; (CLXXXIX) and 1.054; (CLXXXIX) and 1.055; (CLXXXIX) and 1.056; (CLXXXIX) and 1.057; (CLXXXIX) and 1.058; (CXC) and 1.001; (CXC) and 1.008; (CXC) and 1.011; (CXC) and 1.012; (CXC) and 1.013; (CXC) and 1.014; (CXC) and 1.015; (CXC) and 1.018; (CXC) and 1.019; (CXC) and 1.020; (CXC) and 1.021; (CXC) and 1.022; (CXC) and 1.054; (CXC) and 1.055; (CXC) and 1.056; (CXC) and 1.057; (CXC) and 1.058; (CXCL) and 1.001; (CXCL) and 1.008; (CXCL) and 1.011; (CXCL) and 1.012; (CXCL) and 1.013; (CXCL) and 1.014; (CXCL) and 1.015; (CXCL) and 1.018; (CXCL) and 1.019; (CXCL) and 1.020; (CXCL) and 1.021; (CXCL) and 1.022; (CXCL) and 1.054; (CXCL) and 1.055; (CXCL) and 1.056; (CXCL) and 1.057; (CXCL) and 1.058; (A1) and 1.001; (A1) and 1.008; (A1) and 1.011; (A1) and 1.012; (A1) and 1.013; (A1) and 1.014; (A1) and 1.015; (A1) and 1.018; (A1) and 1.019; (A1) and 1.020; (A1) and 1.021; (A1) and 1.022; (A1) and 1.054; (A1) and 1.055; (A1) and 1.056; (A1) and 1.057; (A1) and 1.058; (A2) and 1.001; (A) and 1.008; (A2) and 1.011; (A2) and 1.012; (A2) and 1.013; (A2) and 1.014; (A2) and 1.015; (A2) and 1.018; (A2) and 1.019; (A2) and 1.020; (A2) and 1.021; (A2) and 1.022; (A2) and 1.054; (A2) and 1.055; (A2) and 1.056; (A2) and 1.057; (A2) and 1.058; (A3) and 1.001; (A3) and 1.008; (A3) and 1.011; (A3) and 1.012; (A3) and 1.013; (A3) and 1.014; (A3) and 1.015; (A3) and 1.018; (A3) and 1.019; (A3) and 1.020; (A3) and 1.021; (A3) and 1.022; (A3) and 1.054; (A3) and 1.055; (A3) and 1.056; (A3) and 1.057; (A3) and 1.058; (A4) and 1.001; (A4) and 1.008; (A4) and 1.011; (A4) and 1.012; (A4) and 1.013; (A4) and 1.014; (A4) and 1.015; (A4) and 1.018; (A4) and 1.019; (A4) and 1.020; (A4) and 1.021; (A4) and 1.022; (A4) and 1.054; (A4) and 1.055; (A4) and 1.056; (A4) and 1.057; (A4) and 1.058;(A5) and 1.001; (A5) and 1.008; (A5) and 1.011;(A5) and 1.012;(A5) and 1.013;(A5) and 1.014; (A5) and 1.015; (A5) and 1.018; (A5) and 1.019; (A5) and 1.020; (A5) and 1.021; (A5) and 1.022; (A5) and 1.054; (A5) and 1.055; (A5) and 1.056; (A5) and 1.057; (A5) and 1.058; (A6) and 1.001; (A6) and 1.008; (A6) and 1.011; (A6) and 1.012; (A6) and 1.013; (A6) and 1.014; (A6) and 1.015; (A6) and 1.018; (A6) and 1.019; (A6) and 1.020; (A6) and 1.021; (A6) and 1.022; (A6) and 1.054; (A6) and 1.055; (A6) and 1.056: (A6) and 1.057; (A6) and 1.058; (A10) and 1.001; (A10) and 1.008; (A10) and 1.011; (A10) and 1.012; (A10) and 1.013; (A10) and 1.014; (A10) and 1.015; (A10) and 1.018; (A10) and 1.019; (A10) and 1.020; (A10) and 1.021; (A10) and 1.022; (A10) and 1.054; (A10) and 1.055; (A10) and 1.056; (A10) and 1.057; (A10) and 1.058; (A11) and 1.001; (A11) and 1.008; (All) and 1.011; (A11) and 1.012; (A11) and 1.013; (A11) and 1.014; (A11) and 1.015; (A11) and 1.018; (A11) and 1.019; (A11) and 1.020; (A11) and 1.021; (A11) and 1.022; (A11) and 1.054; (A11) and 1.055; (A11) and 1.056; (A11) and 1.057; (A11) and 1.058; (R1) and 1.001; (R1) and 1.008; (R1) and 1.011; (R1) and 1.012; (R1) and 1.013; (R1) and 1.014; (R1) and 1.015; (R1) and 1.018; (R1) and 1.019; (R1) and 1.020; (R1) and 1.021; (R1) and 1.022; (R1) and 1.054; (R1) and 1.055; (R1) and 1.056; (R1) and 1.057; (R1) and 1.058; (R2) and 1.001; (R2) and 1.008; (R2) and 1.011; (R2) and 1.012; (R2) and 1.013; (R2) and 1.014; (R2) and 1.015; (R2) and 1.018; (R2) and 1.019; (R2) and 1.020; (R2) and 1.021; (R2) and 1.022; (R2) and 1.054; (R2) and 1.055; (R2) and 1.056; (R2) and 1.057; (R2) and 1.058; (R3) and 1.001; (R3) and 1.008; (R3) and 1.011; (R3) and 1.012; (R3) and 1.013; (R3) and 1.014; (R3) and 1.015; (R3) and 1.018; (R3) and 1.019; (R3) and 1.020; (R3) and 1.021; (R3) and 1.022; (R3) and 1.054; (R3) and 1.055; (R3) and 1.056; (R3) and 1.057; (R3) and 1.058; (IX) and 1.059; (IX) and 1.060; (IX) and 1.061; (IX) and 1.062; (IX) and 1.063; (IX) and 1.064; (IX) and 1.065; (IX) and 1.066; (IX) and 1.067; (IX) and 1.068; (IX) and 1.069; (IX) and 1.070; .X) and 1.071; (IX) and 1.072; (IX) and 1.073; (IX) and 1.074; (IX) and 1.075; (IX) and 1.076; (IX) and 1.077; (IX) and 1.078; (IX) and 1.079; (IX) and 1.080; (IX) and 1.081; (IX) and 1.082; (IX) and 1.083; (IX) and 1.084; (IX) and 1.085; (IX) and 1.086; (IX) and 1.087; (XIII) and 1.059; (XIII) and 1.060; (XIII) and 1.061; (XIII) and 1.062; (XIIX) and 1.063; (XIII) and 1.064; (XIII) and 1.065; (XIII) and 1.066; (XIII) and 1.067; (XIII) and 1.068; (XIII) and 1.069; (XIII) and 1.070; (XIII) and 1.071; (XIII) and 1.072; (XIII) and 1.073; (XIII) and 1.074; (XIII) and 1.075; (XIII) and 1.076; (XIII) and 1.077; (XIII) and 1.078; (XIII) and 1.079; (XIII) and 1.080; (XIII) and 1.081; (XIII) and 1.082; (XIII) and 1.083; (XIII) and 1.084; (XIII) and 1.085; (XIII) and 1.086; (XIII) and 1.087; (XIV) and 1.059; (XIV) and 1.060; (XIV) and 1.061; (XIV) and 1.062; (XIV) and 1.063; (XIV) and 1.064; (XIV) and 1.065; (XIV) and 1.066; (XIV) and 1.067; (XIV) and 1.068; (XIV) and 1.069; (XIV) and 1.070; (XIV) and 1.071; (XIV) and 1.072; (XIV) and 1.073; (XIV) and 1.074; (XIV) and 1.075; (XIV) and 1.076; (XIV) and 1.077; (XIV) and 1.078; (XIV) and 1.079; (XIV) and 1.080; (XIV) and 1.081; (XIV) and 1.082; (XIV) and 1.083; (XIV) and 1.084; (XIV) and 1.085; (XIV) and 1.086; (XIV) and 1.087; (LI) and 1.059; (LI) and 1.060; (LI) and 1.061; (LI) and 1.062; (LI) and 1.063; (LI) and 1.064; (LI) and 1.065; (LI) and 1.066; (LI) and 1.067; (LI) and 1.068; (LI) and 1.069; (LI) and 1.070; (LI) and 1.071; (LI) and 1.072; (LI) and 1.073; (LI) and 1.074; (LI) and 1.075; (LI) and 1.076; (LI) and 1.077; (LI) and 1.078; (LI) and 1.079; (LI) and 1.080; (LI) and 1.081; (LI) and 1.082; (LI) and 1.083; (LI) and 1.084; (LI) and 1.085; (LI) and 1.086; (LI) and 1.087; (XXV) and 1.059; (XXV) and 1.060; (XXV) and 1.061; (XXV) and 1.062; (XXV) and 1.063; (XXV) and 1.064; (XXV) and 1.065; (XXV) and 1.066; (XXV) and 1.067; (XXV) and 1.068; (XXV) and 1.069; (XXV) and 1.070; (XXV) and 1.071; (XXV) and 1.072; (XXV) and 1.073; (XXV) and 1.074; (XXV) and 1.075; (XXV) and 1.076; (XXV) and 1.077; (XXV) and 1.078; (XXV) and 1.079; (XXV) and 1.080; (XXV) and 1.081; (XXV) and 1.082; (XXV) and 1.083; (XXV) and 1.084; (XXV) and 1.085; (XXV) and 1.086; (XXV) and 1.087; (XXXV) and 1.059; (XXXV) and 1.060; (XXXV) and 1.061; (XXXV) and 1.062; (XXXV) and 1.063; (XXXV) and 1.064; (XXXV) and 1.065; (XXXV) and 1.066; (XXXV) and 1.067; (XXXV) and 1.068; (XXXV) and 1.069; (XXXV) and 1.070; (XXXV) and 1.071; (XXXV) and 1.072; (XXXV) and 1.073; (XXXV) and 1.074; (XXXV) and 1.075; (XXXV) and 1.076; (XXXV) and 1.077; (XXXV) and 1.078; (XXXV) and 1.079; (XXXV) and 1.080; (XXXV) and 1.081; (XXXV) and 1.082; (XXXV) and 1.083; (XXXV) and 1.084; (XXXV) and 1.085; (XXXV) and 1.086; (XXXV) and 1.087; (XXXVIII) and 1.059; (XXXVIII) and 1.060; (XXXVIII) and 1.061; (XXXVIII) and 1.062; (XXXVIII) and 1.063; (XXXVIII) and 1.064; (XXXVIII) and 1.065; (XXXVIII) and 1.066; (XXXVIII) and 1.067; (XXXVIII) and 1.068; (XXXVIII) and 1.069; (XXXVIII) and 1.070; (XXXVIII) and 1.071; (XXXVIII) and 1.072; (XXXVIII) and 1.073; (XXXVIII) and 1.074; (XXXVIII) and 1.075; (XXXVIII) and 1.076; (XXXVIII) and 1.077; (XXXVIII) and 1.078; (XXXVIII) and 1.079; (XXXVIII) and 1.080; (XXXVIII) and 1.081; (XXXVIII) and 1.082; (XXXVIII) and 1.083; (XXXVIII) and 1.084; (XXXVIII) and 1.085; (XXXVIII) and 1.086; (XXXVIII) and 1.087; (XLI) and 1.059; (XLI) and 1.060; (XLI) and 1.061; (XLI) and 1.062; (XLI) and 1.063; (XLI) and 1.064; (XLI) and 1.065; (XLI) and 1.066; (XLI) and 1.067; (XLI) and 1.068; (XLI) and 1.069; (XLI) and 1.070; (XLI) and 1.071; (XLI) and 1.072; (XLI) and 1.073; (XLI) and 1.074; (XLI) and 1.075; (XLI) and 1.076; (XLI) and 1.077; (XLI) and 1.078; (XLI) and 1.079; (XLI) and 1.080; (XLI) and 1.081; (XLI) and 1.082; (XLI) and 1.083; (XLI) and 1.084; (XLI) and 1.085; (XLI) and 1.086; (XLI) and 1.087; (XLVII) and 1.059; (XLVII) and 1.060; (XLVII) and 1.061; (XLVII) and 1.062; (XLVII) and 1.063; (CIX) and 1.064; (XLVII) and 1.065; (XLVII) and 1.066; (XLVII) and 1.067; (XLVII) and 1.068; (XLVII) and 1.069; (XLVII) and 1.070; (XLVII) and 1.071; (XLVII) and 1.072; (XLVII) and 1.073; (XLVII) and 1.074; (XLVII) and 1.075; (XLVII) and 1.076; (XLVII) and 1.077; (XLVII) and 1.078; (XLVII) and 1.079; (XLVII) and 1.080; (XLVII) and 1.081; (XLVII) and 1.082; (XLVII) and 1.083; (XLVII) and 1.084; (XLVII) and 1.085; (XLVII) and 1.086; (XLVII) and 1.087; (XLIX) and 1.059; (XLVIX) and 1.060; (XLIX) and 1.061; (XLIX) and 1.062; (XLIX) and 1.063; (CIX) and 1.064; (XLIX) and 1.065; (XLIX) and 1.066; (XLIX) and 1.067; (XLIX) and 1.068; (XLIX) and 1.069; (XLIX) and 1.070; (XLIX) and 1.071; (XLIX) and 1.072; (XLIX) and 1.073; (XLIX) and 1.074; (XLIX) and 1.075; (XLIX) and 1.076; (XLIX) and 1.077; (XLIX) and 1.078; (XLIX) and 1.079; (XLIX) and 1.080; (XLIX) and 1.081; (XLIX) and 1.082; (XLIX) and 1.083; (XLIX) and 1.084; (XLIX) and 1.085; (XLIX) and 1.086; (XLIX) and 1.087; (LXI) and 1.059; (LXI) and 1.060; (LXI) and 1.061; (LXI) and 1.062; (LXI) and 1.063; (CIX) and 1.064; (LXI) and 1.065; (LXI) and 1.066; (LXI) and 1.067; (LXI) and 1.068; (LXI) and 1.069; (LXI) and 1.070; (LXI) and 1.071; (LXI) and 1.072; (LXI) and 1.073; (LXI) and 1.074; (LXI) and 1.075; (LXI) and 1.076; (LXI) and 1.077; (LXI) and 1.078; (LXI) and 1.079; (LXI) and 1.080; (LXI) and 1.081; (LXI) and 1.082; (LXI) and 1.083; (LXI) and 1.084; (LXI) and 1.085; (LXI) and 1.086; (LXI) and 1.087; (LXII) and 1.059; (LXII) and 1.060; (LXII) and 1.061; (LXII) and 1.062; (LXII) and 1.063; (CIX) and 1.064; (LXII) and 1.065; (LXII) and 1.066; (LXII) and 1.067; (LXII) and 1.068; (LXII) and 1.069; (LXII) and 1.070; (LXII) and 1.071; (LXII) and 1.072; (LXII) and 1.073; (LXII) and 1.074; (LXII) and 1.075; (LXII) and 1.076; (LXII) and 1.077; (LXII) and 1.078; (LXII) and 1.079; (LXII) and 1.080; (LXII) and 1.081; (LXII) and 1.082; (LXII) and 1.083; (LXII) and 1.084; (LXII) and 1.085; (LXII) and 1.086; (LXII) and 1.087; (CIX) and 1.059; (CIX) and 1.060; (CIX) and 1.061; (CIX) and 1.062; (CIX) and 1.063; (CIX) and 1.064; (CIX) and 1.065; (CIX) and 1.066; (CIX) and 1.067; (CIX) and 1.068; (CIX) and 1.069; (CIX) and 1.070; (CIX) and 1.071; (CIX) and 1.072; (CIX) and 1.073; (CIX) and 1.074; (CIX) and 1.075; (CIX) and 1.076; (CIX) and 1.077; (CIX) and 1.078; (CIX) and 1.079; (CIX) and 1.080; (CIX) and 1.081; (CIX) and 1.082; (CIX) and 1.083; (CIX) and 1.084; (CIX) and 1.085; (CIX) and 1.086; (CIX) and 1.087; (CXIII) and 1.059; (CXIII) and 1.060; (CXIII) and 1.061; (CXIII) and 1.062; (CXIII) and 1.063; (CXIII) and 1.064; (CXIII) and 1.065; (CXIII) and 1.066; (CXIII) and 1.067; (CXIII) and 1.068; (CXIII) and 1.069; (CXIII) and 1.070; (CXIII) and 1.071; (CXIII) and 1.072; (CXIII) and 1.073; (CXIII) and 1.074; (CXIII) and 1.075; (CXIII) and 1.076; (CXIII) and 1.077; (CXIII) and 1.078; (CXIII) and 1.079; (CXIII) and 1.080; (CXIII) and 1.081; (CXXII) and 1.082; (CXIII) and 1.083; (CXIII) and 1.084; (CXIII) and 1.085; (CXIII) and 1.086; (CXIII) and 1.087; (CXIX) and 1.059; (CXIX) and 1.060; (CXIX) and 1.061; (CXIX) and 1.062; (CXIX) and 1.063; (CXIX) and 1.064; (CXIX) and 1.065; (CXIX) and 1.066; (CXIX) and 1.067; (CXIX) and 1.068; (CXIX) and 1.069; (CXIX) and 1.070; (CXIX) and 1.071; (CXIX) and 1.072; (CXIX) and 1.073; (CXIX) and 1.074; (CXIX) and 1.075; (CXIX) and 1.076; (CXIX) and 1.077; (CXIX) and 1.078; (CXIX) and 1.079; (CXIX) and 1.080; (CXIX) and 1.081; (CXIX) and 1.082; (CXIX) and 1.083; (CXIX) and 1.084; (CXIX) and 1.085; (CXIX) and 1.086; (CXIX) and 1.087; (CXXIV) and 1.059; (CXXIV) and 1.060; (CXXIV) and 1.061; (CXXIV) and 1.062; (CXXIV) and 1.063; (CXX) IV) and 1.064; (CXXIV) and 1.065; (CXXIV) and 1.066; (CXXIV) and 1.067; (CXXIV) and 1.068; (CXXIV) and 1.069; (CXXIV) and 1.070; (CXXIV) and 1.071; (CXXIV) and 1.072; (CXXIV) and 1.073; (CXXIV) and 1.074; (CXXIV) and 1.076; (CXXIV) and 1.076; (CXXIV) and 1.077; (CXXIV) and 1.078; (CXXIV) and 1.079; (CXXIV) and 1.080; (CXXIV) and 1.081; (CXXIV) and 1.082; (CXXIV) and 1.083; (CXXIV) and 1.084; (CXXIV) and 1.085; (CXXIV) and 1.086; (CXXIV) and 1.087; (CXXXI) and 1.059; (CXXXI) and 1.060; (CXXXI) and 1.061; (CXXXI) and 1.062; (CXXXI) and 1.063; (CXXXI) and 1.064; (CXXXI) and 1.065; (CXXXI) and 1.068; (CXXXI) and 1.067; (CXXXI) and 1.068; (CXXXI) and 1.069; (CXXXI) and 1.070; (CXXXI) and 1.071; (CXXXI) and 1.072; (CXXXI) and 1.073; (CXXXI) and 1.074; (CXXXI) and 1.075; (CXXXI) and 1.076; (CXXXI) and 1.077; (CXXXI) and 1.078; (CXXXI) and 1.079; (CXXXI) and 1.080; (CXXXI) and 1.081; (CXXXI) and 1.082; (CXXXI) and 1.083; (CXXXI) and 1.084; (CXXXI) and 1.085; (CXXXI) and 1.086; (CXXXI) and 1.087; (CXXXII) and 1.059; (CXXXII) and 1.060; (CXXXII) and 1.061; (CXXXII) and 1.062; (CXXXII) and 1.063; (CXXXII) and 1.064; (CXXXII) and 1.065; (CXXXII) and 1.066; (CXXXII) and 1.067; (CXXXII) and 1.068; (CXXXII) and 1.069; (CXXXII) and 1.070; (CXXXII) and 1.071; (CXXXII) and 1.072; (CXXXII) and 1.073; (CXXXII) and 1.074; (CXXXII) and 1.075; (CXXXII) and 1.076; (CXXXII) and 1.077; (CXXXII) and 1.078; (CXXXII) and 1.079; (CXXXII) and 1.080; (CXXXII) and 1.081; (CXXXII) and 1.082; (CXXXII) and 1.083; (CXXXII) and 1.084; (CXXXII) and 1.085; (CXXXII) and 1.086; (CXXXII) and 1.087; (CXXXIX) and 1.059; (CXXXIX) and 1.060; (CXXXIX) and 1.061; (CXXXIX) and 1.062; (CXXXIX) and 1.063; (CXXXIX) and 1.064; (CXXXIX) and 1.065; (CXXXIX) and 1.066; (CXXXIX) and 1.067; (CXXXIX) and 1.068; (CXXXIX) and 1.069; (CXXXIX) and 1.070; (CXXXIX) and 1.071; (CXXXIX) and 1.072; (CXXXIX) and 1.073; (CXXXIX) and 1.074; (CXXXIX) and 1.075; (CXXXIX) and 1.076; (CXXXIX) and 1.077; (CXXXIX) and 1.078; (CXXXIX) and 1.079; (CXXXIX) and 1.080; (CXXXIX) and 1.081; (CXXXIX) and 1.082; (CXXXIX) and 1.083; (CXXXIX) and 1.084; (CXXXIX) and 1.085; (CXXXIX) and 1.086; (CXXXIX) and 1.087; (A1) and 1.059; (A1) and 1.060; (A1) and 1.061; (A1) and 1.062; (A1) and 1.063; (A1) and 1.064; (A1) and 1.065; (A1) and 1.066; (A1) and 1.067; (A1) and 1.068; (A1) and 1.069; (A1) and 1.070; (A1) and 1.071; (A1) and 1.072; (A1) and 1.073; (A1) and 1.074; (A1) and 1.075; (A1) and 1.076; (A1) and 1.077; (A1) and 1.078; (A1) and 1.079; (A1) and 1.080; (A1) and 1.081; (A1) and 1.082; (A1) and 1.083; (A1) and 1.084; (A1) and 1.085; (A1) and 1.086; (A1) and 1.087; (A2) and 1.059; (A2) and 1.060; (A2) and 1.061; (A2) and 1.062; (A2) and 1.063; (A2) and 1.064; (A2) and 1.065; (A2) and 1.066; (A2) and 1.067; (A2) and 1.068; (A2) and 1.069; (A2) and 1.070; (A2) and 1.071; (A2) and 1.072; (A2) and 1.073; (A2) and 1.074; (A2) and 1.075; (A2) and 1.076; (A2) and 1.077; (A2) and 1.078; (A2) and 1.079; (A2) and 1.080; (A2) and 1.081; (A2) and 1.082; (A2) and 1.083; (A2) and 1.084; (A2) and 1.085; (A2) and 1.086; (A2) and 1.087; (A3) and 1.059; (A3) and 1.060; (A3) and 1.061; (A3) and 1.062; (A3) and 1.063; (A3) and 1.064; (A3) and 1.065; (A3) and 1.066; (A3) and 1.067; (A3) and 1.068; (A3) and 1.069; (A3) and 1.070; (A3) and 1.071; (A3) and 1.072; (A3) and 1.073; (A3) and 1.074; (A3) and 1.075; (A3) and 1.076; (A3) and 1.077; (A3) and 1.078; (A3) and 1.079; (A3) and 1.080; (A3) and 1.081; (A3) and 1.082; (A3) and 1.083; (A3) and 1.084; (A3) and 1.085; (A3) and 1.086; (A3) and 1.087; (A4) and 1.059; (A4) and 1.060; (A4) and 1.061; (A4) and 1.062; (A4) and 1.063; (A4) and 1.064; (A4) and 1.065; (A4) and 1.066; (A4) and 1.067; (A4) and 1.068; (A4) and 1.069; (A4) and 1.070; (A4) and 1.071; (A4) and 1.072; (A4) and 1.073; (A4) and 1.074; (A4) and 1.075; (A4) and 1.076; (A4) and 1.077; (A4) and 1.078; (A4).and 1.079; (A4) and 1.080; (A4) and 1.081; (A4) and 1.082; (A4) and 1.083; (A4) and 1.084; (A4) and 1.085; (A4) and 1.086; (A4) and 1.087; (A6) and 1.059; (A6) and 1.060; (A6) and 1.061; (A6) and 1.062; (A6) and 1.063; (A6) and 1.064; (A6) and 1.065; (A6) and 1.066; (A6) and 1.067; (A6) and 1.068; (A6) and 1.069; (A6) and 1.070; (A6) and 1.071; (A6) and 1.072; (A6) and 1.073; (A6) and 1.074; (A6) and 1.075; (A6) and 1.076; (A6) and 1.077; (A6) and 1.078; (A6) and 1.079; (A6) and 1.080; (A6) and 1.081; (A6) and 1.082; (A6) and 1.083; (A6) and 1.084; (A6) and 1.085; (A6) and 1.086; (A6) and 1.087; (R2) and 1.059; (R2) and 1.060; (R2) and 1.061; (R2) and 1.062; (R2) and 1.063; (R2) and 1.064; (R2) and 1.065; (R2) and 1.066; (R2) and 1.067; (R2) and 1.068; (R2) and 1.069; (R2) and 1.070; (R2) and 1.071; (R2) and 1.072; (R2) and 1.073; (R2) and 1.074; (R2) and 1.075; (R2) and 1.076; (R2) and 1.077; (R2) and 1.078; (R2) and 1.079; (R2) and 1.080; (R2) and 1.081; (R2) and 1.082; (R2) and 1.083; (R2) and 1.084; (R2) and 1.085; (R2) and 1.086; and (R2) and 1.087, preference being given to those combinations in which a partner is underlined.
The following reaction scheme gives a diagrammatic overview of the preparation of the compounds of formula (I): 
The substituents R, R1, R2, R2xe2x80x2, X, Y, T and U indicated in the above scheme are as defined for formula (I); W is a leaving group; Hal is halogen, such as fluorine, chlorine, bromine or iodine, preferably chlorine, bromine or iodine.
Leaving groups W in the compounds of formulae (VI) and (VIII) that are suitable for the reactions are known from the literature and are described, for example, in: Houben-Weyl-Methoden der organischen Chemie, Vol. E4-carbonic acid derivatives (pages 149-165), H. Hagemann (Eds.), Georg Thieme Verag, Stuttgart 1983. Especially preferred leaving groups are halogen, preferably iodine or chlorine; C1-C8alkoxy, C1-C6alkylthio, phenoxy, N-hydroxy-succinimide, N-hydroxy-phthalimide, imidazole, triazoles and 1-hydroxybenzotriazole-N-oxyl. It will be understood that all leaving groups that contain aliphatic or aromatic rings may be unsubstituted or substituted at those rings by customary substituents.
The compounds of formula (XX) are novel except of 1-(1- chloroethoxycarbonyl)-3-(2-chloro-5-thiatOlylmethyl)-1-methyl-2-nitroguanidin, which is described in EP 0471 371 and in JP-A-05 11251. They exhibit a pesticidal spectrum of action similar to that of the compounds of formula (I). The present invention relates to those compounds also. In the compounds of formula (XX), as regards the substituents R1, R2, R2xe2x80x2, X, Y, T and U preference is given to the same substituents as those already mentioned for the preferred sub-groups of compounds of formula (I), Hal preferably being fluorine or chlorine, especially chlorine. As a result of the Hal substituent, these novel compounds are excellently suitable for further derivation and therefore for the preparation of parasiticides, for example the compounds of formula (I).
The reactions illustrated and described hereinabove and hereinbelow are carried out in a manner known per se, for example in the absence or, usually, in the presence of a suitable solvent or diluent or a mixture thereof, the operation being carried out, as required, with cooling, at room temperature or with heating, for example in a temperature range of from about xe2x88x9280xc2x0 C. to the boiling temperature of the reaction medium, preferably from about xe2x88x9240xc2x0 C. to about +120xc2x0 C., especially from xe2x88x9220xc2x0 C. to 40xc2x0 C. and, if necessary, in a closed vessel, under pressure, in an inert gas atmosphere and/or under anhydrous conditions. Especially advantageous reaction conditions for each individual reaction step can be found in the explanations which follow and in the specific Preparation Examples.
Unless special conditions are mentioned, the reactants can in principle be reacted with one another as such, that is to say without the addition of a solvent or diluent, for example in the molten state. It is more advantageous, however, to add an inert solvent or diluent or a mixture thereof. Examples of such solvents or diluents that may be mentioned include: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, Tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, tetrachloromethane, dichloroethane, trichloroethene or tetrachloroethene; esters, such as ethyl acetate; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether, tetrahydroturan or dioxane; ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone; alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, ethylene glycol or glycerol; amides, such as N,N-dimethylformamide, N,N-diethyfformamide, N,N-dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoric acid triamide; nitrites, such as acetonitnle or propionitrile; and sufoxides, such as dimethyl sulfoxide. If the reaction in question is carried out in the presence of a base, bases used in excess, such as triethylamine, pyridine, N-methylmorpholine or N,N-diethylaniline, may also serve as solvent or diluent. If the reaction is carried out in the presence of an acid catalyst, it is also possible to employ as solvent or diluent acids used in excess, e.g. strong organic carboxylic acids, such as unsubstituted or substituted, for example halo-substituted, C1-C4alkanecarboxylic acids, e.g. formic acid, acetic acid or propionic acid. Suitable solvents for the reaction in question can be taken from the Examples given below.
Bases suitable for facilitating those reactions in which base catalysts may optionally be used are, for example, alkali metal or alkaline earth metal hydroxides, hydrides, alkylides, amides, alkanolates, acetates, carbonates, dialkylamides or alkylsilylamides; alkylamines, alkylenediamines, free or N-alkylated, saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and also carbocyclic amines. Examples are butyllithium, sodium hydroxide, sodium hydride, sodium amide, sodium methanolate, sodium acetate, sodium carbonate, potassium tert-butanolate, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and also 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU). For replacing chlorine by iodine in a compound of formula (VI), the base used is preferably silver carbonate and the reagent used sodium iodide.
The procedure in detail is as follows: the compounds of formula (I) are prepared by either (a) reacting a compound of formula (IX) in an aprotic, advantageously polar, solvent in the presence of a suitable base and at relatively low temperatures with a compound of formula (VIII) or preferably (b) reacting a compound of formula (XX) with an acid RCOOH and isolating the end product from the reaction mixture, the substituents R, R1, R2, R2xe2x80x2, X, Y, T and U being as defined for formula (I); W being a leaving group; and Hal being halogen, such as fluorine, chlorine, bromine or iodine, preferably chlorine, bromine or iodine. The reaction is advantageously carried out in an anhydrous medium and under an inert gas atmosphere, for example under nitrogen or argon. The said reactions take place within a period of minutes up to several hours.
A preferred embodiment comprises the following features: the compound of formula (IX) is first dissolved in an anhydrous, aprotic, polar solvent, and then at a relatively low temperature, for example at ambient temperature or lower, an equimolar amount of one of the suitable bases described above, for example sodium hydride, is added and the mixture is stirred for a little longer at the same temperature. An equimolar amount of the compound of formula (VIII) dissolved in the same solvent is then added in portions, e.g. by dropwise addition, and stirring of the reaction mixture is continued at the same low temperature for a little longer. Any excess base is then neutralised and the reaction mixture is stirred for a few minutes longer and finally concentrated. The residue is advantageously taken up in a polar solvent, such as ethyl acetate, and optionally washed with water, and the organic phase is separated off and dried over a drying agent, for example an alkali or alkaline earth metal sulfate or carbonate, preferably magnesium or sodium sulfate, concentrated and purified. A suitable purification step is chromatography, for example on silica gel (ethyl acetate:hexane/1:1). Compounds of formula (I) are generally obtained in the form of colourless to dark yellow oils, resins or in the form of solids. The said oils and resins crystallise after a few days or weeks when stored, for example, in a freezer at about from xe2x88x9218xc2x0 to xe2x88x9225xc2x0 C. In the context of the present invention, relatively low temperatures are to be understood as being temperatures around room temperature and below or a temperature range of from about +25xc2x0 C. to about xe2x88x9280xc2x0 C., preferably from room temperature to about xe2x88x9220xc2x0 C.
The compounds of formula (IX) are known per se from the literature or can be prepared analogously to the examples described in the literature. For example, compounds of formula (IX) wherein Het is pyridyl that is unsubstituted or mono- or poly-substtuted by halogen are described, together with their preparation, in European published specification EP-0 302 833. Further compounds of formula (IX) are disclosed in the following patent references, for example in European published specifications Nos. 285 985; 302 389, 376 279; 471 372; 364 844; 493 369; 381 130; 529 680; 163 855; 375 907; 259 738; 386 565; 383 091 and 590 425; U.S. Pat. Nos. 5,063,236; 5,302,605 and 4,742,060; and also in DE-4 207 604; GB-2 228 003 and WO 93/24002.
The compounds of formula (VIII) wherein R, R2 and R2xe2x80x2 are as defined for formula (I) and W is one of the leaving groups mentioned above can be prepared by introducing the radical RCOOxe2x80x94 into a compound of formula (VI). For that purpose it is advantageous to prepare a suspension of a compound of formula (VI) wherein Hal is iodine and an organic acid Rxe2x80x94COOH, an example of which is benzoic acid, and silver carbonate in an aprotic solvent, e.g. toluene or xylene. The suspension is heated at from about 50xc2x0 C. to about 100xc2x0 C. for a few hours and then the reaction mixture is cooled to room temperature and insoluble constituents are filtered off. The filtrate is washed with water and/or aqueous sodium chloride solution and dried over a customary drying agent, such as magnesium or sodium sulfate. On concentration, the compound of formula (VIII) is obtained in the form of an oil or a crystalline solid. It is generally unnecessary to carry out further purification before use in the next reaction step.
The preparation of compounds of formula (VI) wherein R2 and R2xe2x80x2 are as defined for formula (I), W is one of the leaving groups mentioned hereinabove and Hal is iodine is effected by replacing by iodine the chlorine atom in a compound of formula (VI) wherein Hal is chlorine. For this purpose a suspension of the compound of formula (VI) wherein Hal is chlorine, an equimolar amount of sodium iodide and sodium hydrogen carbonate in a polar solvent, such as acetone, is prepared and is stirred at slightly elevated temperature, about 40xc2x0 C., for from 12 to 24 hours. The resulting precipitate is filtered off and washed with acetone. The filtrate is concentrated, and diethyl ether and water are added. The organic phase is separated off and washed with aqueous potassium sulfite solution, then washed with aqueous sodium chloride solution and dried over a customary drying agent, such as magnesium or sodium sulfate. On concentration, the compound of formula (VI) is obtained in the form of a colourless, crystalline product, which can be filtered off and freed of solvent residues, e.g. in vacua. Further purification before use in the next reaction step is unnecessary.
Compounds of formula (VI) can be prepared by dissolving compounds of formula (VI) wherein R2 and R2xe2x80x2 are as defined for formula (I) and W is chlorine in a halogenated solvent, such as dichloromethane, and at low temperature, advantageously about 0xc2x0 C., adding a solution of a compound of the formula Hxe2x80x94W in portions and then stirring the reaction mixture at the low temperature for about 1 to 3 hours. Water is then added and the organic phase is separated off, washed with 1N sodium hydroxide solution and then with aqueous sodium chloride solution and dried over a drying agent, e.g. magnesium suffate. On concentration, the compound of formula (VI) is obtained in the form of a colourless, crystalline product, which can be filtered off and freed of solvent residues in vacuo.
As illustrated in the above reaction scheme, the novel compounds of formula (XX) are prepared by reacting a compound of formula (IX) in an aprotic, advantageously polar, solvent in the presence of a suitable base and at relatively low temperatures, with a compound of formula (VII), the substituents R1, R2, R2xe2x80x2, X, Y, T and U in the formulae (XX), (IX) and (VI) being as defined for formula (I); W being a leaving group; and Hal being halogen, such as fluorine, chlorine, bromine or iodine and preferably chlorine or iodine. The compound of formula (IX) is first dissolved in an anhydrous, aprotic, polar solvent, and then at relatively low temperature, e.g. ambient temperature or lower, an equimolar amount of one of the suitable bases described above, e.g sodium hydride, is added and the mixture is stirred for a little longer at the same temperature. An equimolar amount of the compound of formula (VI) dissolved in the same solvent is then added in portions, e.g. by dropwise addition, and stirring of the reaction mixture is continued at the same low temperature for a little longer. Any excess base is then neutralised and the reaction mixture is stirred for a few minutes longer and finally concentrated. The residue is advantageously taken up in a polar solvent, such as ethyl acetate, and optionally washed with water, and the organic phase is separated off and dried over a drying agent, for example an alkali or alkaline earth metal sulfate or carbonate, preferably magnesium or sodium sulfate, concentrated and purified. A suitable purification step is chromatography, for example on silica gel (ethyl acetate : hexane/1:1). Compounds of formula (XX) are generally obtained in the form of colourless to dark yellow oils, resins or, predominantly, in the form of solids.